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Biomedical subjects

E Rubinstein

Publications and source records attributed to E Rubinstein.

At least 127 records · Page 7Linked to original sources
PubMed1993

Organization of the human CD9 gene.

The CD9 antigen was originally described as a 24-kDa molecule present on B-lineage-derived acute lymphoblastic leukemia cells and developing B lymphocytes. Platelets also express a large amount of CD9 antigen and can be activated by CD9 antibodies. We report here the structure of the CD9 gene, which is composed of 8 exons spanning more than 20 kb. There is no TATA or CAAT box in the 5'-flanking domain of the CD9 gene, but a 120-bp region extremely rich in C and G (88%) contains several Sp 1 binding sites and a consensus site for the binding of zinc-finger proteins of the Krox/EGR family. The CD9 antigen belongs to a new cell surface protein family. The organization of its gene closely resembles the organization of the genes for two other members of this protein family, TAPA1 and CD63, which share with CD9 respectively 45 and 25% identity at the amino acid level.

Amino Acid Sequence↗
PubMed1993

The IL-2 receptor present on human embryonic fibroblasts is functional in the absence of P64/IL-2R gamma chain.

In this study, we have investigated the IL-2R gamma gene expression in several human embryonic fibroblasts which express other components of the IL-2 receptor (IL-2R). Polymerase chain reaction did not allow us to detect IL-2R gamma transcripts in these cells but the functionality of the IL-2R alpha beta was not affected. Indeed, in the human IL-2R alpha+beta+gamma- embryonic lung fibroblasts ICIG-7, IL-2 induced identical phenomena to those previously reported in lymphoid cells: rapid internalization of the IL-2R alpha beta-IL-2 complex, specific phosphorylation of cellular proteins (56 and 38 kDa) and up-regulation of ICAM-1 expression. IL-2 induction of ICAM-1 was only observed in sparse cultures and for IL-2 concentrations over 180 pM. We have also observed, in these fibroblastic cells, the up-regulation of ICAM-2 expression by IL-2, both in sparse and dense cultures. These data show that p64/IL-2R gamma expression in human embryonic fibroblasts does not correlate with the ability of the IL-2R to deliver a biological signal.

Amino Acid Sequence↗
PubMed1993

Oesophageal and gastric potential difference and pH in healthy volunteers following intake of coca-cola, red wine, and alcohol.

Alcohol causes gastroesophageal reflux and mucosal damage in the oesophagus and the stomach. The transmucosal electrical potential difference gives information on gastric mucosal integrity and function, while the validity of oesophageal measurements have been discussed. Baseline oesophageal potential difference measurements were performed three times with an interval of at least one week. We found oesophageal potential difference measurements reliable with an acceptable reproducibility. Oesophageal and gastric potential difference and pH were measured by use of a new microelectrode principle in 10 healthy volunteers following intake of coca-cola, wine and alcohol. Oesophageal and gastric potential difference decreased after intake of 250 ml coca-cola, 250 ml 11 vol% red wine and 60 ml 43 vol% whisky. Gastric potential difference decreased after intake of 250 ml ethanol 11 vol% and 60 ml ethanol 43 vol%. Intake of red wine and whisky resulted in a significant greater gastric potential difference decrease compared to similar concentrations and volumes of ethanol. The time until the potential difference had regained baseline level was longer after intake of red wine compared to coca-cola, whisky and ethanol. Oesophageal pH decreased after intake of coca-cola and red wine, but was unchanged after whisky. Gastric pH was unchanged after intake of all the drinks. In conclusion, the gastric potential difference reduction was not correlated to alcohol concentration. Red wine seems to affect the gastric potential difference more than coca-cola, whisky and ethanol. The observed changes in oesophageal and gastric potential difference might be due to changes in Cl- secretion and/or due to a damaging effect of the additives of the beverages.

Adult↗
PubMed1993

Therapy of experimental murine brucellosis with streptomycin alone and in combination with ciprofloxacin, doxycycline, and rifampin.

The in vivo efficacy of streptomycin (STR), doxycycline (DOX), rifampin (RIF), ciprofloxacin (CIP), and their combinations was evaluated for a Brucella melitensis experimental infection in a mouse model. Animals were infected with 2 x 10(4) to 4 x 10(4) CFU of B. melitensis intraperitoneally on day 0 and were randomized to receive, starting on day 7, STR alone at 75, 150, or 300 mg/kg of body weight per day intraperitoneally or DOX at 6 mg/kg/day orally, RIF at 3 mg/kg/day orally, or CIP at 200 mg/kg/day orally, each of the last three drugs alone or in combination with STR at 75, 150, or 300 mg/kg/day, for 14 days. Therapy failure (defined as nonsterile spleens) was observed in all animals treated with STR at all doses and with CIP given as monotherapy. Mean log CFU isolated from the spleens remaining infected following monotherapy with STR or CIP were not different from those in control mice. RIF at a low dose did not have an effect on cure rates; however, a reduction in CFU relative to the CFU in untreated animals was obtained. DOX at low levels achieved a 35% cure rate and a reduction in CFU in animals not cured. All animals treated with DOX or RIF combined with any STR dose were cured, but none of the animals receiving the STR-CIP combinations was cured, and the splenic CFU remained similar to those in the controls. These results demonstrate that the combinations DOX-STR and RIF-STR are synergistic against B. melitensis, while the combination STR-CIP is indifferent and ineffective in the management of acute murine brucellosis. The results also appear to support the clinical superiority of combination drug therapy over monotherapy.

Animals↗
PubMed1993

The effect of intravenous omeprazole on the gastric and duodenal potential difference and pH in healthy subjects.

The effect of intravenous omeprazole (40 and 80 mg) on the gastric and duodenal potential difference (PD) and pH was investigated in 9 healthy volunteers. Gastric PD and pH increased significantly (p < 0.05) following omeprazole, and the increases were equal following the two doses. No changes were found in duodenal PD or pH. It has been claimed that gastric PD changes following acid secretion inhibition with cimetidine and glucagon might be due to changes in the parietal cell surface area. Omeprazole causes no changes in the parietal cell structure, and the changes in gastric PD following omeprazole might therefore be ascribed to changes in mucosal electrophysiologic transport or resistance.

Action Potentials↗
PubMed1993

A review of the adverse events profile of cefpirome.

Cefpirome is a new fourth generation injectable cephalosporin antibiotic. Its tolerability profile was established in a programme of 16 clinical studies involving 3103 patients in Europe and the US. The overall incidence of clinical adverse events with cefpirome was 21.9% compared with 27.1% with comparators (ceftazidime, imipenem, ceftriaxone). Adverse events thought possibly related to treatment occurred in 12.5% of patients receiving cefpirome and 13.7% of recipients of comparator agents. Withdrawals from treatment due to adverse events occurred in 5.1 and 5.0% of patients receiving cefpirome and comparators, respectively. The commonest adverse events thought possibly related to treatment were gastrointestinal symptoms (mainly diarrhoea in 1.6 and 1.7%, respectively) and rash (1.4 and 1.4%, respectively). Comparison with data obtained from the literature for ceftazidime, ceftriaxone and the third generation cephalosporins in general shows that the adverse event profile of cefpirome is similar to that of other broad-spectrum injectable cephalosporins.

Cephalosporins↗
PubMed1993

Cost implications of home care on serious infections.

More than 250,000 Americans will receive home IV drug therapy this year. Antibiotics will account for two-thirds of this care. Over 60% of infections treated at home are caused by gram-positive cocci, with staphylococci accounting for approximately 24% of the pathogens. Bone and joint infections represent the most common diagnoses among patients receiving parenteral antibiotics at home, and many of the infections treated at home were initially acquired in the hospital. The most common serious complications of coronary bypass surgery, the most frequently performed operation in many hospitals, are sternal wound infections are methicillin-resistant The major pathogenic causes of these infections are methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. These complications are usually treated with prolonged inpatient IV therapy and surgery. In a study in which patients with sternal wound infections or mediastinitis secondary to coronary bypass surgery were treated with teicoplanin, preliminary results showed that the mean postoperative hospital stay was decreased by more than 7 days compared with patients receiving other types of antibiotic therapy. This was accomplished by changing from intravenous to intramuscular therapy as soon as the patient became stabilized and then discharging the patient after an additional 2 days to complete intramuscular therapy at home. In addition to enhancing the quality of life for the patient by allowing early hospital discharge and early ambulation, home therapy offers the additional benefits of decreasing the risk of cross infection to other patients, as well as to the already infected patient.

Drug Costs↗
PubMed1993

Human melanoma cell line M14 secretes a functional interleukin 2.

Interleukin 2 (IL2) is an important regulator of the immune system. In this report, we have analysed five human melanoma cell lines expressing the IL2R for their ability to secrete IL2. In the M14 melanoma cell line, we observed the appearance of the 0.9 kb transcript specific for the IL2 gene, 72 h after subculture, and the secretion of a biologically active IL2 which specifically sustains the proliferation of the IL2 dependent murine lymphoid cell line CTLL2. In M14 cells, IL2 gene activation is transient as in lymphoid cells but is not inhibited by the immunosuppressive drugs cyclosporine-A and FK506 which are effective on PHA-blasts. In M14 cells, recombinant IL2 (36 pM) induces the down modulation of ICAM-1 expression at the surface of M14 cells. Overnight incubation of these cells with polyclonal anti-IL2 antibodies leads to an increased expression of ICAM-1 and a decreased membrane detection of the IL2R alpha, suggesting the existence of an autocrine/paracrine loop involved in the surface expression of these antigens. A decreased expression of the ICAM-1 protein could help some melanoma cells to escape from cytolytic recognition and therefore favour their metastasis.

Cell Adhesion Molecules↗
PubMed1993

Contraceptive surgery and breast tumors in mice.

The effect of contraceptive surgical manipulations on mammary gland changes was investigated in mice models. Total hysterectomy with bilateral adnexectomy, bilateral tubal ligation, unilateral tubal ligation and moderate uterine compression were performed in various subgroups of 500 mice. Mammary gland tumors (adenomas, adenocarcinomas, squamous cell carcinomas) were observed in an average of 50% (between 20 and 66%) of the operated animals about 6 months after surgery, while the controls remained free of tumors. Surgical interference with the reproductive capacity seems to have an effect on the mammary glands, inducing neoplastic changes. The relationship of our results to the influence of contraceptive procedures on the appearance of mammary gland tumors in women is discussed.

Adenocarcinoma↗
PubMed1992

Platelet activation by cross-linking HLA class I molecules and Fc receptor.

The effect on platelet activation of monoclonal antibodies directed against common determinants of the HLA class I heavy chain molecule was studied. Cross-linking W6/32, an anti-HLA class I of IgG2a subclass, led to platelet activation. Two other antibodies of the same subclass did not have this effect on platelets. The lack of activity of the F(ab')2 fragments suggests that the activation signal is mediated by the platelet Fc receptor (Fc gamma RII). Indeed, except for a higher sensitivity of W6/32 to aspirin and apyrase, activations by cross-linking IV-3 (an anti-Fc gamma RII) and W6/32 are similar at the level of InsP3 formation, calcium mobilization, pH modifications, and activation of protein kinase C and myosin kinase. When HLA class I molecules and Fc gamma RII are cross-linked together, platelet activation occurs. This is not observed when a control IgG2a is substituted for W6/32 or when CD9 and Fc receptor are cross-linked together. This suggests that HLA class I molecules and Fc gamma RII synergize to activate platelets.

Adenosine Diphosphate↗
PubMed1992

Low concentrations of sodium azide specifically inhibit a thromboxane A2 pathway in human platelets.

Sodium azide completely inhibits the serotonin release induced by ADP, arachidonic acid and the thromboxane A2 mimetic U46619, but does not have any effect on the activation by PMA. Collagen and thrombin are inhibited when used at low concentrations, but not at high concentration. This pattern of activation suggests that the inhibition by azide is not a metabolic inhibition. The antagonism of U46619-induced secretion was further studied and was shown to be non-competitive. It is selective for certain components of the U46619 stimulus-response coupling: aggregation, serotonin secretion and the activation of protein kinase C are completely or almost completely inhibited by 300 microM sodium azide. Shape change, calcium elevation, cytoplasmic alkalinization and phosphorylation of myosin light chain are only partially modified. This suggests that azide may specifically inhibit one of the different forms of thromboxane A2 receptors present in platelets.

Adenosine Diphosphate↗
PubMed1992

Expression of the interleukin-2 receptor on human fibroblasts and its biological significance.

In this study, we have investigated the expression of the alpha and beta chains of the IL-2 receptor (IL-2R alpha, IL-2R beta) both at the membrane and at transcriptional levels during the lifespan of human embryonic fibroblasts. Here we show that the mAbs IOT14 and MIK beta 1 directed against the IL-2 binding sites of the IL-2R alpha and IL-2R beta respectively, stain human embryonic fibroblasts early in their life span. Data from [125I]rIL2 cross-linking experiments show the simultaneous expression of two IL-2 binding peptides of 70 and 55 kDa respectively on embryonic young fibroblasts as on lymphoid activated cells. The p55 and the p70 IL-2 binding peptides are shown to be specific for the IL-2R alpha and to the IL-2R beta by the finding that these bands are abolished by excess amounts of cold IL-2 and mAbs directed against the IL-2 binding sites of the alpha and beta chains. Scatchard analysis after [125I]IL-2 labelling shows the presence of both high affinity (150 sites with a Kd of 147 pM) and low affinity (1100 sites with a Kd of 4 nM) IL-2 binding sites. Northern blot and dot blot analysis show the presence of specific transcripts for the IL-2R alpha and IL-2R beta genes in early passaged fibroblasts. By contrast, in senescent cultures, only the IL-2R beta transcript were detected. Finally, IL-2 at low concentrations (36 pM) down modulates the level of the intercellular adhesion molecule ICAM-1 in young but not in senescent cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Adhesion Molecules↗